Asymmetric ring opening of epoxides with cyanides catalysed by chiral binuclear titanium complexes

Article abstract of DOI:10.1016/j.tetasy.2014.04.012

A series of Schiff bases obtained from salicylaldehydes and 3,3′-diformyl-BINOL were synthesized. The complexes of these Schiff bases with Ti(IV) were active for the asymmetric ring opening of epoxides with TMSCN. A mixture of unpurified ligands was found

Full text of DOI:10.1016/j.tetasy.2014.04.012

Tetrahedron: Asymmetry 25 (2014) 838–843
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Asymmetric ring opening of epoxides with cyanides catalysed by
chiral binuclear titanium complexes
⇑
Victor I. Maleev , Denis A. Chusov, Lidiya V. Yashkina, Nikolai S. Ikonnikov, Michail M. Il’in
A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilova Str. 28, 119991 Moscow, Russian Federation
a r t i c l e i n f o
a b s t r a c t
A series of Schiff bases obtained from salicylaldehydes and 3,30-diformyl-BINOL were synthesized. The
complexes of these Schiff bases with Ti(IV) were active for the asymmetric ring opening of epoxides with
TMSCN. A mixture of unpurified ligands was found to be as effective as the best one. The influence of tem-
perature, solvent polarity and structural modification of the pre-catalysts on the enantioselectivity of the
process has also been investigated.
Article history:
Received 25 March 2014
Accepted 17 April 2014
Available online 2 June 2014
Ó 2014 Elsevier Ltd. All rights reserved.
1. Introduction
binaphthols7–10 (Scheme 2). Catalysts were prepared in situ by
mixing ligands with two equivalents of titanium tetraisopropoxide.
The design and use of bi- and polynuclear chiral Lewis acid cat-
alysts for asymmetric catalysis is a rapidly developing area.1 The
rational design of chiral ligands capable of supporting two Lewis
acid sites rigidly oriented in space is straightforward. For example,
Trost’s dinuclear Zn-catalysts have been used for aldol condensa-
tions.2 Some of us have developed highly efficient homobinuclear
Ti-based3 and heteronuclear Ti/V mixed4 chiral catalysts for the
asymmetric addition of cyanides to carbonyl compounds. Such an
approach has been widely used not only in asymmetric catalysis
but also for polymerization reactions.5 Also well known is that sim-
ple mixing of several single-site chiral catalysts can be extremely
successful, leading to efficient heterobimetallic catalysts.6 It is
important to use very pure ligands. We previously described the
binuclear titanium catalyst for cyanations of aldehydes and
meso-epoxides, which can give high ee only when the ligand is very
pure. Even if the NMR spectrum is clean, the elemental analysis
could be bad, meaning that the enantiomeric excess decreased to
20–30%.7 However, it is much easier to use ligands without any
purification. Herein we report on a mixture of unpurified ligands
that can be used for the asymmetric ring-opening of epoxides with
TMSCN.
The asymmetric ring opening of cyclohexene oxide 5 with trim-
ethylsilylcyanide (TMSCN) (Scheme 2) was chosen as a model reac-
tion. It has previously been reported that titanium complexes can
lead to a mixture of nitrile and isonitrile products in the model
reaction.11 Even the diastereomer of a ligand can change the ratio
between the nitrile and isonitrile.12 In order to check the hard and
soft acid-base theory, we prepared catalysts from aluminium and
zinc. The results were in agreement with the theory. Catalysts
based on hard aluminium led exclusively to the nitrile product
while soft zinc led only to the isonitrile product (Table 1, entries
1 and 2). When we switched the metal to the titanium tetraiso-
propoxide, great enantioselectivity was achieved. There were no
significant differences in the activity or nitrile–isonitrile ratio in
the catalysis with the pre-catalysts from ligands 1–3 (Table 1,
entries 3, 4 and 6). However, the enantiomeric excess of the main
product was slightly higher (96%) in case ligand 2 was used.
Decreasing the amount of catalyst from 5 to 1 mol % did not lead
to a decrease in the activity or enantioselectivity but increased
the amount of isonitrile 7 (Table 1, entry 4 vs 5). Since ligand 3
is derived from the inexpensive and highly accessible salicylalde-
hyde, we decided to explore its catalytic ability. Decreasing the
temperature from RT to ꢀ20 °C led to an increase in the enantio-
meric excess of product 6 to 95% (Table 1, entry 6 vs 15). However,
it also led to a decrease in the 6:7 ratio. The catalyst can be used
several times without a loss in enantioselectivity and also with
higher nitrile–isonitrile ratio (Table 1, entries 6–8). On the other
hand, the chemical yield decreased. This could be due to an incor-
rect measurement of the amount of the catalyst after a recycle,
because the structure of the catalyst could be completely different
after the first recycle. Unsymmetrical Schiff bases can be unstable
2. Results and discussion
Ligands 1–4 (see Scheme 1) were prepared as described earlier
from the corresponding racemic and enantiomerically pure
⇑
Corresponding author. Tel./fax: +7 (499) 135 6356.
E-mail address: vim@ineos.ac.ru (V.I. Maleev).
http://dx.doi.org/10.1016/j.tetasy.2014.04.012
0957-4166/Ó 2014 Elsevier Ltd. All rights reserved.

V. I. Maleev et al. / Tetrahedron: Asymmetry 25 (2014) 838–843
839
N
N
N
N
N
OH HO
tBu
OH
OH
HO
HO
tBu
tBu
tBu
OH HO
N
N
N
1
2
N
N
OH HO
N
N
HO
tBu
tBu
OH
tBu
OH HO
tBu
N
N
4
3
Scheme 1. Chiral ligands for catalysis.
O
HO
HO
1. NaH/DMF MOMCl
2. BuLi/TMEDA
R
NH2
1-3
3. DMF
4. HCl
OH
OH
O
Scheme 2. Synthesis of ligands 1–3.
and change equilibrium to increase entropy. We mixed ligands 1
and 2 in a 1:1 ratio. Such a system showed identical results with
pure ligand 2. During the synthesis of ligand 2, a mixture of 1, 2
and 4 was formed. Ligand 4 itself was the most ineffective com-
pared to ligands 1–3 (Table 1, entry 11 vs 3, 4 and 6). We decided
to use this unpurified mixture of Schiff bases with titanium tetra-
isopropoxide as the pre-catalyst. Fortunately, this mixture was
very effective and led to a product with 95% ee. We found that this
mixture of different ligands was very effective for the asymmetric
ring-opening of epoxides with TMSCN. Since the difference in
enantioselectivity was small, we decided to decrease the catalyst
loading to find which ligand was the most effective. When
0.1 mol % of ligands were used, it was shown that only the catalyst
based on ligand 2 remained effective (Table 1, entries 12–14). Even
at 0.1 mol % of ligand 2 the yield after 24 h was 95% and the ee
was 96%. The configuration of BINOL is responsible for the absolute
configuration of the product. When the catalyst derived from
(R)-BINOL was used, (1S,2R)-2-((trimethylsilyl)oxy)cyclohexane-1-
carbonitrile was observed. Furthermore we decided to study the
activity of ligands 2 and 3 for other meso-epoxides. Ligand 2 was
found to be more active but slightly less regioselective than ligand
3 for the ring opening of cyclopentene oxide (Table 2, entry 1 vs 2).
A similar situation was also found with cyclooctadiene oxide (Table 2,
entry 3 vs 5). Ligand 3 proved to be less active but better in terms of
enantioselectivity. No isonitrile was found in both cases. The catalyst
based on ligand 3 was shown to be recyclable, and even led to a
slight increase in the enantioselectivity (Table 2, entry 3 vs 4).
After we had found that these catalysts were effective in the
asymmetric ring opening of meso-epoxides, we decided to check
their activity in the kinetic resolution of racemic epoxides. The
results are summarized in Table 3. When the racemic propylene
oxide was used, ligand 2 was found to be not only more active
but also more regio- and enantioselective (Table 3, entry 1 vs 2).
Decreasing the reaction time from 24 to 5 h did not increase the
ee but the reaction became more regioselective (Table 3, entry 2
vs 3). When the reaction was carried out at ꢀ20 °C instead of room
temperature, the regioselectivity and the enantiomeric excess
decreased (Table 3, entry 4). When styrene oxide was used as a
substrate, both ligands showed good enantioselectivity but the reg-
ioselectivity changed dramatically. When the catalyst was prepared
from ligand
silyl)oxy)propanenitrile
3
the ratio between 3-phenyl-3-((trimethyl-
and 2-phenyl-3-((trimethylsilyl)oxy)
propanenitrile became 50–50 while the catalyst from ligand 2
showed an inverse ratio 10–29 (Table 3, entry 5 vs 6). When epi-
chlorohydrin was used as a starting material, no other regioisomers
were detected (Table 3, entries 7–11). When the reaction was car-
ried out for 4 h instead of 24, the yield decreased from 38% to 20%
while the enantiomeric excess increased from 55% to 63% (Table 3,
entry 7 vs 8). Cooling down the reaction to ꢀ20 °C led to a slight
increase in ee to 70% but the conversion decreases to 9% (Table 3,

840
V. I. Maleev et al. / Tetrahedron: Asymmetry 25 (2014) 838–843
Table 1
Table 3
Catalysis of asymmetric ring-opening of cyclohexene oxide by TMSCNa
Kinetic resolution of racemic epoxides with TMSCNa
OTMS
R
OTMS
OTMS
OTMS
L + 2Ti(OiPr)4
R
O
L + 2Ti(OiPr)4
DCM
TMSCN
+
O
+
+
TMSCN
+
DCM
C
C
N
R
C
N
N
C
rac
N
5
7
6
Entry
R
Ligand
Yield (%)
ee (%)
Entry
Ligand
mol %
Yield (%)
6:7d
100–0
0–100
90–10
92–8
75–25
88–12
96–4
96–4
92–8
93–7
>99–1
77–23
nd
87–13
85–15
ee (%) 6
2-OTMS
2-CN
2-OTMS
2-CN
1
2
3
4
5
6
7
8
3+2Al(OiPr)3
3+2ZnEt2
1
2
2
3
3 recycle 2
3 recycle 3
2+1 1:1
1+2+4 20–60–20
4
3
1
2
3
10
10
5
5
1
5
5
8
5
5
10
0.1
0.1
0.1
5
62
67
23
0
1
CH3
3
2
2
41
60
50
44
50
10
20
38
9
26
60
23
30
3
9
4
84
87
86
83
89
90
63
55
70
76
84
54
64
nd
nd
nd
nd
66
86
—
—
—
—
—
2
>99
>99
>99
>99
77
92
96
96
92
91
92
96
95
40
54
44
96
95
3c
4
2f
14
50
29
0
5
Ph
3
2
3
3
3
3
2
2
1
6
7d
8
ClCH2
55
0
0
0
0
0
8
9
>99
>99
56
20
22
9b
10b,e
11
12
13
10
11
12
13
14
15b
CF3
CH3
—
nd
95
>99
a
Reaction conditions: epoxide (0.39 mmol), TMSCN (0.195 mmol), RT, 24 h,
a
ligand 5 mol %, Ti(OiPr)4 10 mol %, DCM (0.5 ml).
Reaction conditions: 5 (0.195 mmol), TMSCN (0.390 mmol), RT, 24 h, catalyst
(19.5 mol), DCM (0.5 ml).
b
ꢀ20 °C.
l
c
b
5 h.
ꢀ20 °C.
d
c
4 h.
48 h.
5 h.
e
d
The ratio between nitrile and isonitrile was determined by NMR.
f
Recycle of the catalyst.
Table 2
4. Experimental
4.1. General
Catalysis of asymmetric ring-opening of meso-epoxides by TMSCNa
OTMS
OTMS
O
+
C
1H NMR spectra were recorded on a Bruker Avance 300
(300 MHz) and Bruker Avance 400 spectrometers. Chemical shifts
were measured in the d scale relative to the signal of residual pro-
tons of the deuterated solvent. Optical rotations were measured on
a Perkin–Elmer 341 polarimeter in a temperature maintained cell
(l = 5 cm) at 25 °C. The solvent and the sample concentration in
grams per 100 ml were indicated for all compounds. Elemental
analyses of all the synthesized compounds were performed at
the Laboratory of Elemental Analysis of the A.N. Nesmeyanov Insti-
tute of Organoelement Compounds (Russian Academy of Sciences).
Silica gel Kieselgel 60 (Merck) was used. Solvents were purified
according to standard procedures. Enantiomeric purities were
determined with HPLC on Chiralpak IB-3 eluted with mixture hex-
ane/iPrOH (90:10 or 99:1) 1 ml/min and detected at 254 nm. The
ratio between the nitrile and isonitrile was determined by NMR.
N
C
N
L + 2Ti(OiPr)4
DCM
8
TMSCN
11a
+
10a
OTMS
OTMS
O
+
9
C
N
N
C
10b
11b
Entry
Epoxide
Ligand
Yield (%)
10:11
ee (%) 10
1
2
3
4
5
8
8
9
9
9
2
3
3
>99
90
50
40
70
86–14
90–10
100–0
100–0
100–0
91
92
89
92
85
3 recycle
2
a
Reaction conditions: meso-epoxide (0.195 mmol), TMSCN (0.390 mmol), RT,
24 h, catalyst (19.5 lmol), DCM (0.5 ml).
4.2. Synthesis of the Schiff base from di-tert-butylsalicylaldehyde
and (1R,2R)-cyclohexane diamine hydrochloric salt 12
entry 9). When the reaction time was increased to 48 h under
ꢀ20 °C, both the yield and enantioselectivity increased (Table 3,
entry 10). The problem of low yield and moderate enantioselectiv-
ity was solved only when ligand 2 was used instead of ligand 3
(Table 3, entry 11). Ligand 2 showed enantioselectivity (54% ee)
even for the highly electron deficient trifluoropropylene oxide
(Table 3, entry 12).
ClH3N
N
HO
3. Conclusion
A family of binuclear titanium(IV) catalysts based on unsymmet-
rical Schiff bases has been developed and their reusability has been
reported on. A mixture of unpurifiedSchiff bases can be used directly
for the preparation of highly active and stereospecific catalysts.
These properties make them interesting candidates for the catalysis
of other asymmetric reactions and/or polymerizations.
At first, 0.72 g (6.3 mmol) of (1R,2R)-cyclohexane diamine and
0.337 g (6.3 mmol) of NH4Cl were dissolved in 30 ml of methanol.
The reaction mixture was stirred for 15 min and the solvent was
evaporated under vacuum. The formed solid was washed with
diethyl ether and dissolved in 25 ml of methanol. A solution of

V. I. Maleev et al. / Tetrahedron: Asymmetry 25 (2014) 838–843
841
1.47 g (6.3 mmol) of 3,5-di-tert-butylsalycilaldehyde in 25 ml of
dry methanol was added to the solution. The reaction mixture
was stirred for 15 min and the solvent was evaporated under vac-
uum. To the formed yellow oil 10 ml of diethyl ether was added.
Next, 40 ml of diethyl ether was added and white precipitate was
filtered and dried. Yield 0.99 g (50%). 1H NMR (400 MHz, MeOD)
d 8.60 (s, 1H), 7.43 (d, J = 2.3 Hz, 1H), 7.26 (d, J = 2.3 Hz, 1H),
3.20–3.40 (m, 2H), 2.10–2.22 (m, 1H), 1.80–1.95 (m, 3H), 1.60–
1.75 (m, 1H), 1.45–1.60 (m, 4H), 1.43 (s, 9H), 1.31 (s, 9H).
(400 MHz, CDCl3) d 13.79 (br s, 2H), 13.12 (br s, 2H), 8.55 (s, 2H),
8.20 (s, 2H), 7.84 (s, 2H), 7.75 (d, J = 8.1 Hz, 2H), 7.31 (d,
J = 2.4 Hz, 2H), 7.21 (t, J = 7.4 Hz, 2H), 7.15 (t, J = 7.4 Hz, 2H), 7.04
(d, J = 8.4 Hz, 2H), 6.89 (d, J = 2.4 Hz, 2H), 3.35–3.47 (m, 2H),
3.16–3.30 (m, 2H), 1.80–2.05 (m, 4H), 1.60–1.80 (m, 4H), 1.35–
1.50 (m + s, 13H), 1.19 (s, 9H). 13C NMR (101 MHz, CDCl3) d
165.9, 165.2, 158.0, 154.5, 140.0, 136.4, 135.1, 133.6, 128.7,
128.2, 127.5, 126.9, 125.9, 124.7, 123.2, 120.7, 117.8, 116.3, 73.3,
71.7, 35.0, 34.0, 33.3, 32.8, 31.4, 29.7, 29.4, 24.3, 22.7.
[a
]
D
25 = ꢀ386 (c 0.5, CHCl3).
4.3. Synthesis of ligand 1
4.5. Synthesis of ligand 3
N
N
N
N
HO
HO
OH
OH
OH HO
HO
N
N
N
OH
N
A mixture of 0.26 g (0.979 mmol) of (1R,2R)-cyclohexane dia-
mine mono- -tartrate and 0.27 g (1.958 mmol) of potassium car-
L
1H NMR (300 MHz, CDCl3) d 13.20 (br s, 4H), 8.51 (s, 2H), 8.18 (s,
2H), 7.99 (s, 2H), 7.75–8.05 (m, 4H), 7.33–7.16 (m, 4H), 7.01 (dd,
J = 14.2, 7.9 Hz, 4H), 6.92 (d, J = 8.2 Hz, 2H), 6.78 (t, J = 7.4 Hz,
2H), 3.30 (m, 4H), 2.03–1.37 (m, 16H). 13C NMR (300 MHz, CDCl3)
d 13.20 (s, 4H), 8.50 (s, 2H), 8.18 (s, 2H), 7.85 (s, 2H), 7.81 (d,
J = 7.8 Hz, 2H), 7.31–7.16 (m, 6H), 7.01 (dd, J = 12.4, 8.0 Hz, 4H),
6.90 (d, J = 8.2 Hz, 2H), 6.78 (t, J = 7.4 Hz, 2H), 3.41–3.30 (m, 2H),
bonate was dissolved in 3 ml of 50% aqueous ethanol solution.
The resulting mixture was added to a suspension of 0.335 g
(0.979 mmol) of (R)-3,30-diformyl-BINOL in 7 ml of ethanol. The
reaction mixture was stirred at room temperature for 24 h. The
resulting precipitate was filtered of and washed with ethanol and
dried under vacuum. Yield of light-yellow solid was 0.5 g (61%).
1H NMR (400 MHz, CDCl3) d 13.21 (br s, 4H), 8.47 (s, 4H), 7.75
(m, 8H), 7.28 (m, 4H), 6.96 (m, 8H), 3.31 (m, 4H), 1.82–1.92 (m,
3.29–3.18 (m, 2H), 2.00–1.34 (m, 16H). [
a]
25 = ꢀ352 (c 0.62, CHCl3).
D
8H), 1.40–1.61 (m, 8H). [
a]
25 = ꢀ214 (c 0.25, CH2Cl2).
D
4.6. Synthesis of ligand 4
4.4. Synthesis of ligand 2
N
N
N
N
OH HO
OH HO
HO
Ligand 4 was synthesized according to the literature proce-
dure.13 The binuclear titanium complex was also synthesized
according to the literature procedure.3
N
OH
N
4.7. Asymmetric ring-opening of meso-epoxides with TMSCN
(general procedure)
At first, Ti(O-i-Pr)4 (11.4
ll, 39.0 lmol) was added to a solution
To a solution of 0.2 g (0.6 mmol) of (R)-3,30-diformyl-BINOL and
0.4 ml (2.8 mmol) of triethylamine in 15 ml of dry dichlorometh-
ane was added 0.52 g (1.4 mmol) of 12 at 0 °C under argon. The
reaction mixture was warmed up to 25 °C and stirred for 48 h, until
no starting dialdehyde was found on TLC. The reaction mixture was
worked up with a saturated solution of ammonium chloride in
water, and then extracted with DCM. The organic layer was dried
over anhydrous sodium sulfate, evaporated under vacuum and
purified by column chromatography. Rf = 0.34 (hexane–ethyl
acetate–triethylamine 9:1:0.1). Yield 0.14 g (24%). 1H NMR
of ligands 1–3 (19.5 mol) in absolute DCM (0.5 ml) under an
l
argon atmosphere. The reaction mixture was stirred for 1 h at
room temperature. A clear solution was formed in the case of the
complex from ligand 2, while a suspension was formed in the case
of the complex from ligands 1 or 3. An epoxide (195 mmol) was
then added to the reaction mixture. After 15 min TMSCN
(390 lmol) was added. The colour of the reaction mixture changed
to dark orange. After the indicated time, hexane (or petroleum
ether) (3 ml) was added. The precipitated complex was filtered
off and used for the recycle. The solution was filtered through silica

842
V. I. Maleev et al. / Tetrahedron: Asymmetry 25 (2014) 838–843
gel and evaporated under vacuum. The reaction mixture was ana-
lysed by GC to determine the enantiomeric excess of the nitrile.
(m, 1H). Chiral GC column b-DM 30 m, T(column) = 150 °C, He
15 psi, split ratio 75:1 T(evaporator) = 200 °C, T(detector) = 200 °C,
Tr (minor) = 17.2 min, Tr (major) = 19.5 min. The absolute configu-
ration was assigned and by analogy with 2-((trimethyl-
silyl)oxy)cyclohexane-1-carbonitrile.
4.7.1. 2-((Trimethylsilyl)oxy)cyclohexane-1-carbonitrile
OTMS
4.7.6. 8-((Trimethylsilyl)oxy)cyclooct-4-ene-1-isonitrile
C
N
OTMS
1H NMR (CDCl3) d 0.17 (s, 9H), 1.25–1.33 (m, 3H), 1.55–1.75 (m,
3H), 1.90–2.07 (m, 1H), 2.08–2.11 (m, 1H), 2.38–2.44 (m, 1H),
3.64–3.70 (m, 1H); 13C NMR (CDCl3) d 0.18, 23.3, 23.9, 28.2, 34.7,
37.7, 71.1, 121.6. Chiral GC column b-DM 30 m, T(col-
umn) = 120 °C, He 15 psi, split ratio 75:1 T(evaporator) = 200 °C,
T(detector) = 200 °C, Tr (minor) = 15.0 min, Tr (major) = 15.8 min.
The absolute configuration was determined by chiral GC and
compared to our previous work.12 When the catalyst derived from
(R)-BINOL was used the (1S,2R)-2-((trimethylsilyl)oxy)cyclohex-
ane-1-carbonitrile was observed; with the catalyst derived from
(S)-BINOL the (1R,2S)-2-((trimethylsilyl)oxy)cyclohexane-1-carbo-
nitrile was observed in all cases.
N
C
1H NMR (CDCl3) d 0.17 (s, 9H); 1.50–2.60 (m, 8H); 3.77–3.88
(m, 1H); 3.90–4.00 (m, 1H); 5.49–5.70 (m, 2H).
4.8. Asymmetric kinetic resolution of epoxides with TMSCN
(general procedure)
At first, Ti(O-i-Pr)4 (11.4
ll, 39.0 lmol) was added to a solution
of the ligands 1–3 (19.5 mol) in absolute DCM (0.5 ml) under an
argon atmosphere. The reaction mixture was stirred for 1 h at
room temperature. A clear solution was formed in the case of the
complex from ligand 2, a suspension was formed in the case of
the complex from ligands 1 or 3. An epoxide (390 mmol) was then
l
4.7.2. 2-((Trimethylsilyl)oxy)cyclohexane-1-isonitrile
OTMS
added to the reaction mixture. After 15 min, TMSCN (195 lmol)
was added. The colour of the reaction mixture is changed to dark
orange. After the indicated time, hexane (or petroleum ether)
(3 ml) was added. The precipitated complex was filtered off and
used for the recycle. The solution was filtered through celite and
evaporated under vacuum. The reaction mixture was analysed by
GC to determine the enantiomeric excess of the nitrile.
N
C
1H NMR (CDCl3) d 0.2 (s, 9H), 1.25–1.33 (m, 3H), 1.55–1.75
(m, 3H), 1.90–2.07 (m, 1H), 2.08–2.11 (m, 1H), 3.30–3.35 (m, 1H),
3.60–3.65 (m, 1H); 13C (CDCl3) 0.27, 23.0, 23.2, 31.3, 33.4, 58.7,
72.9, 155.1.
4.8.1. 4,4,4-Trifluoro-3-((trimethylsilyl)oxy)butanenitrile
4.7.3. 2-((Trimethylsilyl)oxy)cyclopentane-1-carbonitrile
OTMS
F
OTMS
F
CN
F
C
N
1H NMR (300 MHz, CDCl3) d 4.30–4.45 (m, 1H), 2.70–2.90 (m,
2H), 0.24 (s, 9H). Chiral GC DP-TFA- -CD column, gas carrier N2
1.8 atm, T = 100 °C. TR = 1.24 and 1.33 min.
1H NMR (CDCl3) d 0.15 (s, 9H), 1.40–2.30 (m, 6H), 2.55–2.70 (m,
1H), 4.36 (dd, J = 11.7, 5.7 Hz, 1H); Chiral GC column b-DM 30 m,
T(column) = 100 °C, He 15 psi, split ratio 75:1 T(evapora-
tor) = 200 °C, T(detector) = 200 °C, Tr (minor) = 18.8 min, Tr
(major) = 19.9 min. The absolute configuration was assigned by
analogy with 2-((trimethylsilyl)oxy)cyclohexane-1-carbonitrile.
c
4.8.2. 3-Phenyl-3-((trimethylsilyl)oxy)propanenitrile
OTMS
CN
Ph
4.7.4. 2-((Trimethylsilyl)oxy)cyclopentane-1-isonitrile
1H NMR (300 MHz, CDCl3) d 7.50–7.35 (m, 5H), 5.05 (m, 1H),
2.73 (AB-part from ABX, JAB = 16.5, JAX = 5.4, JBX = 6.9, 2H), 0.18 (s,
9H). 13C NMR (75 MHz, CDCl3) d 141.7, 128.5, 128.1, 127.8, 125.4,
70.6, 29.4, ꢀ0.2. Chiral HPLC: IB-3 column, 1 ml/min, UV detector
254 nm, hexane–iPrOH 95:5, Tr = 7.8 and 8.2 min. Chiral GC col-
umn b-DM, T(column) = 140 °C, He 15 psi, T(evaporator) = 200 °C,
T(detector) = 200 °C, Tr (minor) = 18.1 min, Tr (major) = 18.7 min.
OTMS
N
C
1H NMR (CDCl3) d 0.14 (s, 9H), 1.30–2.20 (m, 6H), 3.55–3.65 (m,
1H), 4.15–4.25 (m, 1H).
4.7.5. 8-((Trimethylsilyl)oxy)cyclooct-4-ene-1-carbonitrile
4.8.3. 2-Phenyl-3-((trimethylsilyl)oxy)propanenitrile
OTMS
CN
OTMS
Ph
C
N
1H NMR (300 MHz, CDCl3) d 7.50–7.35 (m, 5H), 3.90–4.10
(m, 3H), 0.17 (s, 9H). 13C NMR (75 MHz, CDCl3) d 132.6, 128.8,
128.3, 128.2, 127.8, 65.3, 41.0, ꢀ0.8. Chiral HPLC: IB-3 column,
1H NMR (CDCl3) d 0.17 (s, 9H); 1.80–2.40 (m, 8H); 3.00–3.09 (m,
1H); 3.89 (td, J = 7.90, 3.33 Hz, 1H); 5.50–5.62 (m, 1H); 5.68–5.79

V. I. Maleev et al. / Tetrahedron: Asymmetry 25 (2014) 838–843
843
1 ml/min, UV detector 254 nm, hexane–iPrOH 95:5, Tr = 5.0 and
5.6 min. Chiral GC: column b-DM, T(column) = 140 °C, He 15 psi,
T(evaporator) = 200 °C, T(detector) = 200 °C, Tr (minor) = 20.3 min,
Tr (major) = 20.7 min.
Presidium Russian Academy of Science (Russia). We gratefully
thank PIM Invest for the trifluoropropylene oxide provided for
research. We gratefully thank Professor Yuri N. Belokon for useful
discussion.
References
4.8.4. 4-Chloro-3-((trimethylsilyl)oxy)butanenitrile
1. Matsunaga, S.; Shibasaki, M. Synthesis 2013, 45, 421–437; Ma, J.-A.; Cahard, D.
Angew. Chem., Int. Ed. 2004, 43, 4566–4583; Shibasaki, M.; Kanai, M.;
Funabashi, K. Chem. Commun. 2002, 1989–1999; Shibasaki, M.; Yoshikawa, N.
Chem. Rev. 2002, 102, 2187–2209; Molenveld, P.; Engbersen, J. F. J.; Reinhoudt,
D. N. Chem. Soc. Rev. 2000, 29, 75–86; van den Beuken, E. K.; Feringa, B. L.
Tetrahedron 1998, 54, 12985–13011; Shibasaki, M.; Sasai, H.; Arai, T.; Iida, T.
Pure Appl. Chem. 1998, 70, 1027–1034; Wheatley, N.; Kalck, P. Chem. Rev. 1999,
99, 3379–3419.
OTMS
Cl
CN
1H NMR (300 MHz, CDCl3) d 4.17–4.06 (m, 1H), 3.52 (dd,
J = 13.2, 6.7 Hz, 1H), 3.46 (dd, J = 13.2, 8.8 Hz, 1H), 2.71 (dd,
J = 16.7, 4.5 Hz, 1H), 2.61 (dd, J = 16.7, 6.5 Hz, 1H), 0.19 (s, 9H). Chi-
2. Trost, B. M.; Frederiksen, M. U.; Papillon, J. P. N.; Harrington, P. E.; Shin, S.;
Shireman, B. T. J. Am. Chem. Soc. 2005, 127, 3666–3667.
ral GC DP-TFA-c-CD column, gas carrier N2 1.8 atm, T = 100 °C.
TR = 4.48 and 5.08 min.
3. Belokon, Y. N.; Caveda-Cepas, S.; Green, B.; Ikonnikov, N. S.; Khrustalev, V. N.;
Larichev, V. S.; Moscalenko, M. A.; North, M.; Orizu, C.; Tararov, V. I.; Tasinazzo,
M.; Timofeeva, G. I.; Yashkina, L. V. J. Am. Chem. Soc. 1999, 121, 3968–3973.
4. Belokon, Y. N.; North, M.; Maleev, V. I.; Voskoboev, N. V.; Moskalenko, M. A.;
Peregudov, A. S.; Dmitriev, A. V.; Ikonnikov, N. S.; Kagan, H. B. Angew. Chem., Int.
Ed. 2004, 43, 4085–4089.
4.8.5. 3-((Trimethylsilyl)oxy)butanenitrile
OTMS
CN
5. Delferro, M.; Marks, T. J. Chem. Rev. 2011, 111, 2450–2485.
6. Ohori, K.; Ohshima, T.; Shibasaki, M. Tetrahedron 2002, 2585–2588; Kumagai,
N.; Matsunaga, S.; Kinoshita, T.; Harada, S.; Okada, S.; Sakamoto, S.; Yamaguchi,
K.; Shibasaki, M. J. Am. Chem. Soc. 2003, 125, 2169–2178.
7. For the synthesis of dialdehyde from BINOL see: Belokon, Y. N.; Chusov, D.;
Borkin, D. A.; Yashkina, L. V.; Dmitriev, A. V.; Katayev, D.; North, M.
Tetrahedron: Asymmetry 2006, 17, 2328–2333.
1H NMR (300 MHz, CDCl3) d 4.16–4.06 (m, 1H), 2.45 (d,
J = 5.9 Hz, 2H), 1.28 (d, J = 6.1 Hz, 3H), 0.15 (s, 9H). Chiral GC col-
umn b-DM 30 m, T(column) = 140 °C, He 15 psi, T(evapora-
tor) = 200 °C, T(detector) = 200 °C, Tr (minor) = 18.1 min, Tr
(major) = 18.7 min. Chiral GC Fusedsil 25 m ꢁ 0.23 mm ID column,
gas carrier N2 1.8 atm, T = 100 °C. TR = 1.70 and 1.85 min.
8. For the synthesis of ligand
1 see (a) Srimurugan, S.; Viswanathan, B.;
Varadarajana, T. K.; Varghese, B. Org. Biomol. Chem. 2006, 4, 3044–3047; (b)
Jin, L.; Huang, Y.; Jing, H.; Chang, T.; Yan, P. Tetrahedron: Asymmetry 2008, 19,
1947–1953.
9. For the synthesis of ligand 2 see (a) Ye, L.; Ren, W.-M.; Liu, J.; Lu, X.-B. Angew.
Chem., Int. Ed. 2013, 52, 11594–11598; (b) Widger, P. C. B.; Ahmed, S. M.;
Hirahata, W.; Thomas, R. M.; Lobkovsky, E. B.; Coates, G. W. Chem. Commun.
2010, 2935–2937.
4.8.6. 2-Methyl-3-((trimethylsilyl)oxy)propanenitrile
10. For the synthesis of ligand 4 see Belokon, Yu. N.; Caveda-Cepas, S.; Green, B.;
Ikonnikov, N. S.; Khrustalev, V. N.; Larichev, V. S.; Moscalenko, M. A.; North, M.;
Orizu, C.; Tararov, V. I.; Tasinazzo, M.; Timofeeva, G. I.; Yashkina, L. V. J. Am.
Chem. Soc. 1999, 121, 3968.
11. Hayashi, M.; Tamura, M.; Oguni, N. Synlett 1992, 663–664.
12. Belokon, Yu. N.; Chusov, D.; Peregudov, A. S.; Yashkina, L. V.; Timofeeva, G. I.;
Maleev, V. I.; North, M.; Kagan, H. B. Adv. Synth. Catal. 2009, 351, 3157–3167.
13. Larrow, J. F.; Jacobsen, E. N. Org. Synth. 2004, 10, 96.
CN
OTMS
1H NMR (300 MHz, CDCl3) d 3.66 (t, J = 6.0 Hz, 1H), 2.55–2.50
(m, 2H), 1.36 (d, J = 6.2 Hz, 3H), 0.15 (s, 9H).
Acknowledgments
This work was financially supported by the RFBR Grant #13-03-
90600-ARM-a (Russia) and P-7 Program of Basic Research of